NM_001059.3:c.888+3086C>T

Variant names:

• chr4-103653108-G-A
• rs3796962
• NM_001059.3:c.888+3086C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001059.3(TACR3):​c.888+3086C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 151,858 control chromosomes in the GnomAD database, including 14,714 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (14714 hom., cov: 31)
• Consequence: TACR3 NM_001059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666
• Publications: 3 publications found

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 11 with or without anosmia

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TACR3	NM_001059.3	c.888+3086C>T		intron_variant	Intron 3 of 4	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TACR3	ENST00000304883.3	c.888+3086C>T		intron_variant	Intron 3 of 4	1	NM_001059.3	ENSP00000303325.2

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62032 AN: 151740 Hom.: 14675 Cov.: 31

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.257

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.337

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62120 AN: 151858 Hom.: 14714 Cov.: 31 AF XY: 0.401 AC XY: 29728 AN XY: 74184

African (AFR) AF: 0.664 AC: 27501 AN: 41408

American (AMR) AF: 0.323 AC: 4924 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1065 AN: 3466

East Asian (EAS) AF: 0.257 AC: 1327 AN: 5166

South Asian (SAS) AF: 0.297 AC: 1427 AN: 4812

European-Finnish (FIN) AF: 0.240 AC: 2527 AN: 10540

Middle Eastern (MID) AF: 0.338 AC: 98 AN: 290

European-Non Finnish (NFE) AF: 0.325 AC: 22047 AN: 67926

Other (OTH) AF: 0.397 AC: 836 AN: 2108

Alfa AF: 0.348 Hom.: 38521

Bravo AF: 0.425

Asia WGS AF: 0.305 AC: 1060 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.40
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3796962; hg19: chr4-104574265;